IntroductionMeasurement-based care (MBC) is a structured approach to collecting patient-reported outcome measures (PROMs) to inform clinical care. While MBC is routinely used in mental health settings, its application in neurodevelopmental populations—particularly those with co-occurring physical and mental health conditions—remains limited.MethodsMBC was implemented across three Ontario hospital Extensive Needs Service (ENS) sites in Toronto, Hamilton, and Ottawa. Selection of PROMs was informed by a focused literature review and consultation with clinicians, researchers, and family advisors. A logic model was developed to guide evaluation and link measures to anticipated outcomes. Clinicians received training and support to integrate PROMs into clinical workflows. Data were collected at baseline and at regular intervals.ResultsBetween April 2023 and April 2025, 381 participants entered the ENS program, and 36 were discharged. Their duration of participation ranged from 3 to 20 months. Each site engaged clinical staff in PROM completion. Completion rates for measures were higher at baseline and declined over time. Shorter PROMs showed higher completion rates compared to longer ones.DiscussionThis novel implementation of MBC provides important insights for MBC in pediatric populations with high complexity. Early and ongoing engagement of both clinicians and families is important to success, which is also closely tied to the degree to which MBC is integrated into care processes. MBC remains necessary to guide clinical care and treatment planning for children with complex, intersecting needs. It is also helpful when evaluating new programs and generating foundational evidence on the effectiveness of therapies for this population.

The present study examined how the frequency and impact of autism traits were associated with parent-reported family experience, with differential consideration of parental experience and overall family life. Prior research has found an association between autism traits and family functioning; however, less is known about how the impact and frequency of these traits influence family experience. We analyzed data from families of 206 young autistic children (144 boys and 62 girls), aged 2-7, using the Autism Impact Measure (AIM) and the Autism Family Experience Questionnaire (AFEQ). Hierarchical regression analysis showed that the impact of autistic traits was significantly associated with parent experience scores and that the frequency of autistic traits was significantly associated with family life scores in the first-year post-diagnosis. Neither child age nor gender was significantly associated with parent experience or family life. This study highlights the importance of tailoring post-diagnosis family supports to the child's specific features and calls attention to areas for future investigation on this topic, including the exploration of longitudinal trends or demographic factors that may affect parent experience and family life.

Introduction Autistic children can experience elevated levels of emotional and behavioural problems, which adversely impact their psychosocial functioning. Positive parenting behaviours can significantly shape children’s emotional and behavioural developmental trajectories. However, for autistic children, these parenting behaviours may vary depending on their social, sensory and intellectual profiles. Literature on the association between parenting behaviours and autistic children’s internalising and externalising symptoms has been mixed. Thus, the main objective of this study will be to conduct a systematic review and meta-analysis of studies evaluating the effect of parenting behaviours on autistic children’s internalising and externalising symptoms.Methods and analysis Included studies have child samples between ages 6 and 17 years and a primary diagnosis of autism/Autism Spectrum Disorder (ASD), pervasive developmental disorder and/or Asperger’s syndrome as well as a measure of parenting behaviour. Primary outcomes are internalising and externalising symptoms. Substantive and methodological moderators will be examined. Searches will be conducted in MEDLINE, PsycINFO, Embase, Education Resources Information Center (ERIC) and ProQuest Dissertations and Theses Global from their inception onwards, and we will also conduct backward/forward searching of eligible studies. Published and unpublished studies will be examined. Two independent reviewers will conduct title/abstract and full-text screening as well as data extraction. Risk of bias will be assessed using the Newcastle-Ottawa Quality Assessment Scale and JBI Critical Appraisal tools. A random-effects meta-analysis model will be used, and summary effect sizes will be calculated. Moderation will be examined via Q-statistics and meta-regression to determine factors contributing to between-study variation in effect sizes.Ethics and dissemination Ethics approval is not required, as this review will use secondary data from published studies. Results will be disseminated through a peer-reviewed publication and conference presentations. The protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024528043).Systematic review registration PROSPERO CRD42024528043.

Behavioral inflexibility (BI) is a known challenge for many Autistic individuals and refers to rigid behavioral patterns not easily adapted across changing situations. While the associations between BI and specific autism characteristics are established, research on the possible impact of young children’s BI on familial functioning is limited. To fill the gap, the current study explored the associations between BI and parent-reported family experiences. Participants were 132 families with an Autistic child (M = 3.73 years, SD = 0.84); sample size was determined sufficient to detect a medium effect size (i.e., 0.06 < R2 < 0.11). Measures included the Behavioral Inflexibility Scale (BIS), Autism Family Experience Questionnaire (AFEQ), Autism Impact Measure—communication subscale (AIM), and a sociodemographic questionnaire. After controlling for socioeconomic status, sex, and social-communication symptom severity, (with Benjamini–Hochberg correction), BI was not significantly associated with parenting an Autistic child, but was significantly associated with family life. Our mixed findings may be partially due to the young age of our sample. It is possible that an association between BI and specific family experiences, such as parenting experiences, may not emerge until later years but this needs to be examined. Further understanding of the relationship between BI and family experiences, notably the developmental trajectory of this relationship, may inform understanding of social dynamics, familial supports, and resources for families with Autistic children.

Introduction The developmentally variable nature of autism poses challenges in providing timely services tailored to a child’s needs. Despite a recent focus on longitudinal research, priority-setting initiatives with stakeholders highlighted the importance of studying a child’s day-to-day functioning and social determinants of health to inform clinical care. To address this, we are conducting a pragmatic multi-site, patient-oriented longitudinal investigation: the Pediatric Autism Research Cohort (PARC) Study. In young children (<7 years of age) newly diagnosed with autism, we will: (1) examine variability in trajectories of adaptive functioning from the point of diagnosis into transition to school; and (2) identify factors associated with trajectories of adaptive functioning.Methods and analysis We aim to recruit 1300 children under 7 years of age with a recent (within 12 months) diagnosis of autism from seven sites: six in Canada; one in Israel. Participants will be followed prospectively from diagnosis to age 8 years, with assessments at 6-month intervals. Parents/caregivers will complete questionnaires administered via a customized online research portal. Following each assessment timepoint, families will receive a research summary report describing their child’s progress on adaptive functioning and related domains. Analysis of the longitudinal data will map trajectories and examine child, family and service characteristics associated with chronogeneity (interindividual and intraindividual heterogeneity over time) and possible trajectory turning points around sensitive periods like the transition to school.Ethics and dissemination Ethics approvals have been received by all sites. All parents/respondents will provide informed consent when enrolling in the study. Using an integrated knowledge translation approach, where stakeholders are directly engaged in the research process, the PARC Study will identify factors associated with trajectories of functioning in children with autism. Resulting evidence will be shared with government policy makers to inform provincial and national programs. Findings will be disseminated at conferences and published in peer-reviewed journals.

In the context of developmental trajectories, the association between adaptive functioning and core autism symptomatology remains unclear. The current study examines the associations of adaptive behavior with autism symptom sub-domains and with different facets of symptom expression. Participants include 36 children with a recent diagnosis of autism (33 males; mean age = 56.4 months; SD = 9 months). Families were recruited in the context of the Pediatric Autism Research Cohort (PARC) project. Parents filled out questionnaires at two time points, six months apart, regarding their child’s autism symptoms and adaptive functioning. The longitudinal relationship between adaptive functioning and autism symptoms was investigated using Mixed Linear Model analyses: one assessing the relationship between general symptom levels and adaptive functioning, and another examining the associations between symptom frequency and impact with adaptive functioning. We conducted Pearson correlation tests at both time points to assess the associations between symptom sub-domains and adaptive functioning. Findings showed that higher autism symptoms associated with lower adaptive behavior skills, and that this association remained stable over time. Autism impact scores did not significantly relate to adaptive skills, as opposed to frequency scores. Associations between adaptive functioning and autism symptom sub-domains strengthened over time. These findings suggest that adaptive functioning is associated with parent-report autism symptomatology, and that this association changes and, on average, becomes stronger over time. Findings may indicate that frequency and impact of symptoms have differential roles in the development of adaptive skills and are worthy of further exploration.

BackgroundSocial ABCs is a caregiver-mediated Naturalistic Developmental Behavioral Intervention for toddlers with confirmed/suspected Autism Spectrum Disorder (ASD), with evidence in controlled research settings. Information is lacking on implementation in community settings. We reported on the treatment effectiveness of this program within a community setting, and the current paper describes the implementation phase of this work. Distinguishing between treatment and implementation effectiveness is critical for transporting interventions from laboratory to community.ObjectivesDescribe the implementation of Social ABCs through a large public autism service, supported by a research-community partnership.MethodsWe describe this project through the Exploration, Preparation, Implementation, Sustainment (EPIS) framework as it focuses on implementation of evidence-based practices in publicly funded services. We apply this framework to the reporting stage. This project took place in the context of a 3-year government-funded pilot at a hospital-based publicly funded autism service. Participants: Program developers; Autism Service team; toddlers with suspected/confirmed ASD aged 14–34 months (M = 25.18 months) and their caregivers. Training/supervision: Provided by program developers at tapering intensity. Evaluation: Caregivers completed the Caregiver Diary and satisfaction surveys. We explored training processes, intervention uptake, acceptability, adaptations to fit community context, appropriateness, perceived impact, and facilitators/barriers.ResultsSix coaches were trained to fidelity, and three of these were further trained as Site Trainers. 183 clinically referred families enrolled and 89.4% completed the 12-week program. Caregivers reported increases in adherence and competence, high satisfaction and perceived benefits for their children. Coaches reported high satisfaction. Toddlers were appropriately identified to receive the intervention. Referral processes improved, including decreased referral age, and increased family readiness for diagnostic assessment and subsequent services.ConclusionsSocial ABCs was successfully implemented in a community service through a research-community partnership. The program was feasible, acceptable, and appropriate within a community context. Drivers of success included funding, institutional support, shared decision-making, adaptations to fit context, leadership support, perceived positive impact, and commitment to evaluation.

IntroductionPrevalence rates of emotional and behavior problems (EBP) in autistic children and youth are high (40–70%), and often cause severe and chronic impairment. Furthermore, autistic children are also more likely to experience family “social-ecological” adversity compared to neurotypically developing peers, including social isolation, child maltreatment, caregiver mental illness, and socioeconomic risk. These family stressors increase the risk of co-occurring EBP among autistic children and can often impede access to evidence-based care, thus amplifying long-term health inequities for autistic children and their caregivers. In the current autism services landscape, there are few scalable, evidence-based programs that adequately address these needs. The Family Check-Up (FCU®) is a brief, strength-based, and tailored family-centered intervention that supports positive parenting and explicitly assesses the social determinants of child and family mental health within an ecological framework. Studies have demonstrated long-term positive child and caregiver outcomes in other populations, but the FCU® has not been evaluated in families of autistic children and youth. Therefore, we aimed to evaluate FCU® implementation within an established, publicly funded Autism Program in Ontario, Canada, with delivery by autism therapists, to demonstrate sustainable effectiveness within real-world settings.MethodsIn this study, we outline the protocol for a hybrid implementation-effectiveness approach with two key components: (1) A parallel-arm randomized controlled trial of N = 80 autistic children/youth (ages 6–17 years) and high levels of EBP and their caregivers. Primary and secondary outcomes include child EBP, and caregiver well-being and parenting. (2) A mixed methods implementation study, to describe facilitators and barriers to implementation of the FCU® within an autism service setting.DiscussionScalable, ecologically focused family-centered interventions offer promise as key components of a public health framework aimed at reducing mental health inequities among autistic children, youth, and their caregivers. Results of this study will inform further program refinement and scale-up.

Background We present genomic and phenotypic findings of a transgenerational family consisting of three male offspring, each with a maternally inherited distal 220 kb deletion at locus 16p11.2 (BP2-BP3). Genomic analysis of all family members was prompted by a diagnosis of autism spectrum disorder (ASD) in the eldest child, who also presented with a low body mass index. Methods All male offspring underwent extensive neuropsychiatric evaluation. Both parents were also assessed for social functioning and cognition. The family underwent whole-genome sequencing. Further data curation was undertaken from samples ascertained for neurodevelopmental disorders and congenital abnormalities. Results On medical examination, both the second and third-born male offspring presented with obesity. The second-born male offspring met research diagnostic criteria for ASD at 8 years of age and presented with mild attention deficits. The third-born male offspring was only noted as having motor deficits and received a diagnosis of developmental coordination disorder. Other than the 16p11.2 distal deletion, no additional contributing variants of clinical significance were observed. The mother was clinically evaluated and noted as having a broader autism phenotype. Conclusion In this family, the phenotypes observed are most likely caused by the 16p11.2 distal deletion. The lack of other overt pathogenic mutations identified by genomic sequencing reinforces the variable expressivity that should be heeded in a clinical setting. Importantly, distal 16p11.2 deletions can present with a highly variable phenotype even within a single family. Our additional data curation provides further evidence on the variable clinical presentation among those with pathogenetic 16p11.2 (BP2-BP3) mutations.

Recent efforts have focused on developing and evaluating early intervention for toddlers with probable or emerging autism spectrum disorder. Parent-mediated approaches have gained traction, with mounting evidence of efficacy, but a research-to-practice gap exists, and community effectiveness remains to be firmly established. We report outcomes of a parent-mediated toddler intervention delivered through a research-community partnership, using a community-partnered participatory framework. Data were available for 179 of 183 toddler-parent dyads receiving Social ABCs parent coaching (mean toddler age: 25.18 months; range, 14–34 months). Of these, 89.4% completed the 12-week program and 70.6% returned for 3-month follow-up assessment. Parents attained implementation fidelity exceeding 75%, and toddlers made gains on proximal and distal measures of social communication. Parent fidelity was associated with toddlers’ responsivity at week 12, and responsivity predicted later language gains and reduced autism spectrum disorder symptoms. The roles of child, family, and system factors are discussed. Community delivery of an evidence-based parent-mediated intervention for toddlers with autism spectrum disorder is feasible and effective. Given resource efficiencies associated with parent-mediated approaches, findings bolster current efforts to promote earlier and more widespread access to intervention at the first signs of developmental concern. Lay abstract In an effort to increase access to intervention as early as possible for toddlers with autism spectrum disorder or signs thereof, many researchers have developed interventions that can be delivered by parents in their own homes. These parent-mediated approaches have gained a lot of research attention in recent years and have been found to be helpful in terms of parent and toddler learning. Several studies have used a rigorous research design (a randomized controlled trial) to show that parent-mediated intervention can work under ideal well-controlled conditions. To build on this evidence, we also need to examine whether parent-mediated interventions can be taught well through community service providers and delivered in more “real-world” conditions. This study used a research-community partnership to provide a parent-mediated intervention (called the Social ABCs) to 179 families (mean toddler age was 25 months; ranging from 14 to 34 months). Almost 90% of the families completed the 12-week program and 70% returned for a follow-up assessment 3 months later. Analyses showed that parents learned the strategies that were designed to help them support their toddlers’ development. Also, toddlers made gains in their language, communication, and social skills. Importantly, parents’ use of the strategies was related to toddlers’ skill gains, suggesting that the use of the strategies made a difference for the toddlers. Findings support the use of parent-mediated intervention in this very young age group and suggest that such intervention approaches should be made available for community delivery.

Microduplication of the LCR22-A to LCR22-D region on chromosome 22q11.2 is a recurrent copy number variant found in clinical populations undergoing chromosomal microarray, and at lower frequency in controls. Often inherited, there is limited data on intellectual (IQ) and psychological functioning, particularly in those individuals ascertained through a family member rather than because of neurodevelopmental disorders. To investigate the range of cognitive-behavioral phenotypes associated with 22q11.2 duplication, we studied both probands and their non-proband carrier relatives. Twenty-two individuals with 22q11.2 duplication (10 probands, 12 non-proband carriers) were prospectively assessed with a battery of neuropsychological tests, physical examination, and medical record review. Assessment measures with standardized norms included IQ, academic, adaptive, psychiatric, behavioral, and social functioning. IQ and academic skills were within the average range, with a trend toward lower scores in probands versus non-probands. Adaptive skills were within age expectations. Prevalence of attention deficits (probands only) and anxiety (both groups) was high compared with norms. The prevalence of autism spectrum disorder was relatively low (5% of total sample). Assessment of both probands and non-probands with 22q11.2 duplication suggests that the phenotypic spectrum with respect to neurodevelopment overlaps significantly with the general population. IQ and academic abilities are in the average range for most of the individuals with 22q11.2 duplication in our study, regardless of ascertainment as a proband or non-proband relative. Symptoms of attention deficit and anxiety were identified, which require further study. Results of this study further clarify the phenotype of individuals with 22q11.2 duplication, and provides important information for genetic counseling regarding this recurrent copy number variant.

Objective: The day-to-day experience of families with an Autistic child may be shaped by both, child characteristics and available resources, which often are influenced by the socioeconomic context of the family. Using a socioecological approach, this study explored the quantitative associations between child autistic symptoms, family socioeconomic status, and family life. Methods: Data came from the Pediatric Autism Research Cohort—PARC Study (pilot). Parents of children with a recent diagnosis of autism completed a set of assessments, including the Autism Family Experience Questionnaire, Autism Impact Measure, and a Sociodemographic Questionnaire. A series of multiple, iterative linear regression models were constructed to ascertain quantitative associations between child autistic symptoms, socioeconomic context, and family life. Results: A total of 50 children (mean age: 76 months; SD: 9.5 months; and 84% male) with data on the variables of interest were included in the analysis. The frequency of child autistic symptoms was associated with family life outcomes ( p = 0.02 and R 2 = 24%). Once autistic symptom frequency, symptom impact, and sociodemographic variables were considered, parents of higher educational attainment reported worse family life outcomes compared to their lesser-educated counterparts. This cumulative regression model had considerable explanatory capability ( p = 0.01, R 2 = 40%). Conclusion: This study demonstrates the utility of using a socioecological approach to examine the dynamic interplay between child characteristics and family circumstances. Our findings suggest that family life for parents (of an autistic child) who have obtained higher education is reported (by the parents themselves) as less satisfactory compared to that of parents without higher education, once adjusted for the autistic symptom frequency of child, symptom impact, and income. These findings can inform the design and delivery of more family-centered care pathways during the years following a diagnosis of autism.

The Per family of genes functions as a primary circadian rhythm maintenance in the brain. Mutations in PER2 are associated with familial advanced sleep-phase syndrome 1 (FASPS1), and recently suggested in delayed sleep phase syndrome and idiopathic hypersomnia. The detection of PER2 variants in individuals with autism spectrum disorder (ASD) and without reported sleep disorders, has suggested a role of circadian-relevant genes in the pathophysiology of ASD. It remains unclear whether these individuals may have, in addition to ASD, an undiagnosed circadian rhythm sleep disorder. The MSSNG database was used to screen whole genome sequencing data of 5,102 individuals with ASD for putative mutations in PER2. Families identified were invited to complete sleep phenotyping consisting of a structured interview and two standardized sleep questionnaires: the Pittsburgh Sleep Quality Index and the Morningness-Eveningness Questionnaire. From 5,102 individuals with ASD, two nonsense, one frameshift, and one de novo missense PER2 variants were identified (0.08%). Of these four, none had a diagnosed sleep disorder. Three reported either a history of, or ongoing sleep disturbances, and one had symptoms highly suggestive of FASPS1 (as did a mutation carrier father without ASD). The individual with the missense variant did not report sleep concerns. The ASD and cognitive profiles of these individuals varied in severity and symptoms. The results support a possible role of PER2-related circadian rhythm disturbances in the dysregulation of sleep overall and sometimes FASPS1. The relationship between dysregulated sleep and the pathophysiology of ASD require further exploration.

Objectives The current study evaluated the use of MYmind, a concurrent mindfulness program in which youth with autism and their parents simultaneously receive group specific mindfulness training. Youth with autism can experience emotional and behavioral challenges, which are associated with parental stress. Mindfulness-based programs are emerging as a promising support for these challenges, for both children and parents. While two studies have documented the use of concurrent parent-child programs, neither involve control conditions. Methods Using a within-subject repeated measures design with a baseline component, 23 parent-child dyads were assessed on mindfulness, mental health, and youth emotion regulation and autism symptoms. Participants also rated their perceived improvement on a social validity questionnaire. Results There was improvement in youth autism symptoms, emotion regulation, and adaptive skills, and in parent reports of their own mindfulness following the program. There was also some indication of a waitlist effect for parent mental health, but not for other outcome variables. Participant feedback was mainly positive. Conclusions MYmind has the potential to contribute to emotion regulation and adaptability in youth with autism, and mindfulness in parents, though more rigorous controlled trials are needed.

Seven unrelated individuals (four pediatric, three adults) with the TUBB3 E410K syndrome, harboring identical de novo heterozygous TUBB3 c.1228 G>A mutations, underwent neuropsychological testing and neuroimaging. Despite the absence of cortical malformations, they have intellectual and social disabilities. To search for potential etiologies for these deficits, we compared their brain's structural and white matter organization to 22 controls using structural and diffusion magnetic resonance imaging. Diffusion images were processed to calculate fractional anisotropy (FA) and perform tract reconstructions. Cortical parcellation-based network analysis and gyral topology-based FA analyses were performed. Major interhemispheric, projection and intrahemispheric tracts were manually segmented. Subjects had decreased corpus callosum volume and decreased network efficiency. While only pediatric subjects had diffuse decreases in FA predominantly affecting mid- and long-range tracts, only adult subjects had white matter volume loss associated with decreased cortical surface area. All subjects showed aberrant corticospinal tract trajectory and bilateral absence of the dorsal language network long segment. Furthermore, pediatric subjects had more tracts with decreased FA compared with controls than did adult subjects. These findings define a TUBB3 E410K neuroimaging endophenotype and lead to the hypothesis that the age-related changes are due to microscopic intrahemispheric misguided axons that are pruned during maturation.

De novo loss-of-function (LoF) variants in the KMT2A gene are associated with Wiedemann−Steiner Syndrome (WSS). Recently, de novo KMT2A variants have been identified in sequencing studies of cohorts of individuals with neurodevelopmental disorders (NDDs). However, most of these studies lack the detailed clinical information required to determine whether those individuals have isolated NDDs or WSS (i.e. syndromic NDDs). We performed thorough clinical and neurodevelopmental phenotyping on six individuals with de novo KMT2A variants. From these data, we found that all six patients met clinical criteria for WSS and we further define the neurodevelopmental phenotypes associated with KMT2A variants and WSS. In particular, we identified a subtype of Autism Spectrum Disorder (ASD) in five individuals, characterized by marked rigid, repetitive and inflexible behaviours, emotional dysregulation, externalizing behaviours, but relative social motivation. To further explore the clinical spectrum associated with KMT2A variants, we also conducted a meta-analysis of individuals with KMT2A variants reported in the published literature. We found that de novo LoF or missense variants in KMT2A were significantly more prevalent than predicted by a previously established statistical model of de novo mutation rate for KMT2A. Our genotype−phenotype findings better define the clinical spectrum associated with KMT2A variants and suggest that individuals with de novo LoF and missense variants likely have a clinically unrecognized diagnosis of WSS, rather than isolated NDD or ASD alone. This highlights the importance of a clinical genetic and neurodevelopmental assessment for individuals with such variants in KMT2A.

Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in <0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are NRXN1, SEH1L, LDLRAD4, GNAL, GNG13, MKRN1, DCTN2, KNDC1, PCMTD2, KIF5A, SYNM, and long non-coding RNAs: AK127244 and PTCHD1-AS. We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants.

AbstractLife course health development (LCHD) incorporates theories and empirical evidence from the biological, physical, and social sciences to formulate a framework that explains how health develops over the life course. The life course health development conceptual framework can be applied to autism spectrum disorders (ASD) to help prioritize a research agenda and improve health development across the lifespan for individuals with ASD, their families, and communities. The following chapter highlights some issues and findings that are pertinent to an understanding of ASD using the lens of the life course health development principles. The chapter begins with a description of the clinical phenotype, followed by epidemiology of the disorder, and reviews changes in classification and diagnosis over time. Pathogenesis of the disorder is discussed, including information pertaining to hereditability, genetic and nongenetic factors, epigenetics, biomarkers, and genotype-phenotype correlations. Long-term follow-up outcome studies of adult independence and quality of life are reviewed, including examination of predictors of outcome, as well as stability of the diagnosis, symptom presentation, and cognitive functioning over time. Areas of key transitions over the life course are discussed from childhood to later adulthood. In addition, the importance of mental health status and care are highlighted. Finally, a number of research, data/methods, and translational priorities are offered that may help lead to a better understanding of life course health development in ASD.

OBJECTIVE Executive function (EF) deficits in patients with autism spectrum disorder (ASD) are ubiquitous and understudied. Further, there are no effective, neuroscience-based treatments to address this impairing feature of ASD. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated promise in addressing EF deficits in adult neuropsychiatric disorders. This article will outline the design of a novel randomized-controlled trial of bilateral, 20 Hz, rTMS applied to the dorsolateral prefrontal cortex (DLPFC) for treatment of EF deficits in ASD that is currently ongoing. We describe prior therapeutic rTMS research for ASD and prior rTMS trials targeting EFs in adult neuropsychiatric disorders. A neurophysiological rationale for rTMS treatment of EF deficits in ASD is presented. METHODS An ongoing protocol will enroll participants aged 16-35 with ASD and no intellectual disability. Psychotropic medications will be continued during the 4-week trial of active 20 Hz versus sham rTMS applied to the DLPFC. Twenty, active treatment sessions consisting of 25 stimulation trains at a 90% motor threshold will be administered. The primary outcome measure is the Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial working memory task. At present, recruitment, enrollment, and treatment within the described clinical trial are ongoing. CONCLUSIONS EF deficits are common and impairing symptoms of ASD. There are no evidence-based treatments for EF deficits in ASD. The protocol described here will provide important preliminary data on the feasibility and efficacy of 20 Hz rTMS to DLPFC for EF deficits in ASD.

Yuen et al. developed a cloud-based database with 5,205 whole genomes from families with autism spectrum disorder (ASD). They identified 18 new candidate ASD-risk genes and approximately 100 risk genes and copy-number loci, which account for 11% of the cases. They also found that individuals bearing mutations in ASD-risk genes had lower adaptive ability. We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (P = 6 × 10−4). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.